Drug discovery and

development

Sri Noegrohati
Fac. Of Pharmacy, Sanata Dharma Univ
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Research Topic for Pharmacist

 Pharmacy: the art, practice, or profession of preparing, preserving,
compounding, and dispensing medical drugs  Pharmacists play a vital role in
medication use and patient care to the research process.
 research topics for institutional pharmacists:
• basic pharmaceutical sciences, including the development and testing of
new dosage forms or medication-administration modalities
• clinical research concerning the efficacy, safety, and pharmacokinetics of
drugs
• pharmacy practice research addressing various issues such as the evaluation
of new and existing services, workload measurement, pharmacoeconomics, and
quality management
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Pharmaceutical Research Topic

1. Basic pharmaceutical sciences, creation of revolutionary novel pharmaceuticals from a
foundation of basic research, including the development and testing of new dosage forms or
medication-administration modes
• new drug discoveries,  focuses on the basic chemistry, biology, and pharmacology
of drugs  develop new drugs and drug delivery systems, as well as to improve the
understanding of how drugs work in the body  cures untreated illnesses or medications
with fewer side effects for the better of patients.
Pharmaceutical scientists have various roles from designing or implementing protocols to
conduct trials for studying or comparing effectiveness and safety of new medications before
its launch into markets
• manufacturing technologies to ens ure the manufacturing process of me dications adhere
to strict standards (cGMP) for quality assurance (QA) purposes. Through QA, they ensure
that the final product contains the active ingredient(s) as intended, and at the correct
amount or proportion.  have the assurance that the effect of the medication is consistent
and safe for patients’ consumption
• Generally, does not involve people  types: Pharmaceutical laboratory research; Data
collection: mostly by experimental methods.
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Pharmaceutical Research Topic

2. clinical research focuses on the use of medications in patients, contribute to the care of
the patients in chronic disease management, optimization of medications, concerning the
efficacy, safety, and pharmacokinetics of drugs. Pharmacists conduct clinical research to
evaluate the safety, efficacy, and cost-effectiveness of medications, as well as to develop
new strategies for medication management
• involves people who volunteer to help us better understand medicine and health. Data
collection: can be by randomized controlled trials or experimental methods
3. pharmacy practice research addressing various health services issues such as the
organization, delivery, and financing of healthcare services, quality of the management and
what happens to patients as a result of this care. Examining how and why people access
pharmacy services, workload measurement, counselling drug information for patients,
health professionals, as well as the general public. Pharmacists can conduct health services
research to evaluate the impact of pharmacy services on patient outcomes and healthcare
costs.
• a specialty field within the wider area of health services research . Data collection: can
be by observational or survey method.
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Pharmaceutical R&D
 Pharmaceutical R&D refers to the pharmaceutical research and development of
new medicines. The process begins with understanding the disease and
selecting a target (usually a receptor site on a cell) that can potentially be affected
by a drug molecule (Institute of Medicine 2007; PhRMA 2009).
 Characteristic in genetics, environment, lifestyle  Every person is unique
accompanied by the complexity of human biology  drug development is
challenging.
 However, with the advances in science, data, analytics, computation, and digital
technology  more understand the factors that affect each person’s health with
more clarity than ever before  more possibility to overcome the challenge
 The Role of Research and development of an innovative drugs
• discovering,
• producing, and
• marketing innovative drugs and medical devices — is the pharma industry’s
lifeblood.
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Drug Discovery and Development

 Pharmaceutical R&D refers to the pharmaceutical research and development of new
medicines. The process begins with understanding the disease and selecting a target
(usually a receptor site on a cell) that can potentially be affected by a drug molecule (Institute
of Medicine 2007; PhRMA 2009).
 Generally, the R&D process includes basic and translational research, in addition to
medicines and vaccine development:
• Basic research: Investigates the biological underpinnings of disease and potential
therapeutic targets. Performed by academic research centres, government agencies, and
industry, often in close collaboration with one another.
• Translational research: Connects new knowledge about a process or compound to a
practical medical application or therapy. Typically performed by biopharmaceutical
companies.
• Medicine and vaccine development: Investigates the safety and efficacy of new
medicines and vaccines through clinical trials. Typically performed by biopharmaceutical
companies.
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From molecule/biopharmaceuticals to medicine

Once a company has chosen which disease area to research  study to understand
the underlying problem  select a target ( ) within a biochemical pathway, such
as an enzyme or a receptor, where inhibition or stimulation may lead to changes
which result in treatment of the disease.
1. Pre-clinical research and discovery of innovative drugs
• Finding the best compound from an infinite molecules
• Developing new treatments
2. Clinical trials: Clinical testing of prescription drugs in trials for its efficacy and
safety
1. Preparation and submission of applications for Official approval
2. Designing processes for grand scale of the new product
3. Clinical testing of the new medicinal drug against an existing drug to show
the new product’s superior benefits
4. Additional clinical trials after a new drug reaches the market for safety
monitoring and for possible additional side effects detection
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R&D Process
1 2
Pharmaceutical Research and Manufacturers of America, Drug Discovery and Development: Understanding the R&D
Process, www.innovation.org.
1. basic studies to understand the disease as
thoroughly as possible—its cause or causes,
its natural development, and its impacts on the
entire human body  select a target for a
potential medicine (in vitro)  lead compound
3  safety tests  formulation? Delivery
mechanism
2. Conduct many laboratory studies and tests in
animals  candidate compound is suitable to
be tested in humans?
3. Candidate medicine is tested in human
volunteers: Phase 1 test a in a small group (20 to
100) of healthy volunteers  safety of the
compound? Phase 2 involve a larger group (100
to 500) have the disease or condition under
study  effectiveness of the medicine, possible
short-term side effects and risks, and
determine optimal dose and schedule. Phase 3
a much larger group (1,000 to 5,000) 
statistical information about safety,
effectiveness, and the overall benefit-risk ratio
of the medicine.
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Example: HIV-AIDs case

In the last centuries, Diseases considered fatal, or incurable have been overcome by modern
therapeutic agents.
• The most notable accomplishments was noticed in the consequences of Human
Immunodeficiency Virus (HIV) infection which caused acquired immune deficiency
syndrome (AIDS).
• the virus was first identified by Gallo et al. (1983) and Barre-Sinousi (1983)
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Infection Progress
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target for a
potential
medicine
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Modern Drug Discovery and Development of

Antiretroviral
• There were few antiviral agents available  none provided effective treatment for HIV
infection  infection progressed rapidly to AIDS  finally death by opportunistic
infection.
• By 1987, AZT® (Retrovir®, azidothymidine,), the first reverse transcriptase
inhibitor, was approved for clinical application for the treatment of HIV infection,
• the next three decades, the discovery of modern antiviral drugs such as Viread®
(Tenofovir), Zeffix® (Lamivudine) (reverse transcriptase inhibitors), Viracept®
(Nelfinavir), Norvir® (Ritonavir), and Crixivan® (Indinavir) (HIV protease inhibitors)
provided additional treatment alternatives.
• In the late 1990s, multidrug cocktail treatment regimens enhancing treatment
options, known as Highly Active Antiretroviral Therapy (HAART), such as
Complera® and Stribild®. were introduced
•
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Developing an HIV vaccine

• Challenge:
• no recovered patients  cannot mimic the immune responses
• Inactivated HIV was not effective at eliciting immune responses
• Developing HIV vaccine from two complementary angles:
• an empirical approach  quickly moves vaccine candidates into human testing:
Karasavvas et al. (2012) reported The Thai Phase III HIV Type 1 Vaccine Trial
(RV144) Regimen Induces Antibodies that target Conserved Regions Within the V2
Loop of gp120 contributed to viral attachment inhibition in Thailand, but not in
Southern Africa (Gray et al., CROI 2022).
• a theoretical approach that designs vaccine candidates based on an
understanding of the immune response to HIV infection  Scientists are studying
the design and delivery of antigens-vaccine components that stimulate specific
immune responses-to develop vaccine candidates that may induce HIV-negative
people's immune systems to make Broadly neutralising antibodies (bNAbs) 
prevention
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Emerging Role of Biopharmaceutical

The term ‘biopharmaceutical’ was originally coined to define therapeutic proteins
produced by genetic engineering, rather than by extraction from normal biological
sources  broadened with time, encompasses nucleic acids as well as proteins,
vaccines as well as therapeutic agents, and even cell-based therapies.
• In general, then, biopharmaceuticals require less investment in discovery
technologies than do conventional drugs, because
• The usual starting point for biopharmaceuticals is a naturally occurring peptide,
protein or nucleic acid
• Nature has already done the job, the target identification and validation,
generally unnecessary, or at least streamlined at the outset,.
• biopharmaceuticals toxicity associated with reactive metabolites is uncommon
• Generally, two main areas, namely production methods and formulation require
greater investment than conventional drugs
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Emerging Role cont’d

• Generally, two main areas, namely production methods and formulation require
greater investment than conventional drugs
• Production methods rely on employing biological systems to do the work of
synthesis, and the problems of yield, consistency and quality control are more
complex than they are for organic synthesis.
• Formulation problems arise commonly because biomolecules tend to be large
and unstable, and considerable creativity is often needed to improve their
pharmacokinetic properties, and to target their distribution in the body to where their
actions are required.
• More complex ‘second-generation’ biopharmaceutical ideas for example, using
antisense nucleic acids, ribozymes or RNAi to reduce gene expression, the use of
catalytic antibodies to control chemical reactions in specific cells or tissues,
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Research question
• A research question is an actual question about a particular topic which need an
answer
• To create a research question:
• Pick a topic you are interested in  HIV vaccine
• Narrow the topic to a particular aspect  cause of RV144 trial not effective in
South Africa, while in Thailand reducing 31% HIV infection among vaccinees
• Brainstorm some questions around your topic aspect.
• Select a question to work with.
• Focus the question by making it more specific. Make sure your question clearly
states who (differences in gene?), what (HIV strain?), when (Time of admission?),
where (differences in environment?), and why (the same RV 144 vaccine gave
different result).
•A good research question focuses on one issue only and requires analysis.
•The hypothesis should be a directed to answer the research question, summarized
into one sentence.
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Decide:
• Research design?
• Research design type?
• Research Method?